PD-1 antibody plus chemotherapy in low PD-L1 expressing esophageal squamous cell carcinoma
1. The post-hoc analysis of JUPITER-06 showed the superiority of adding toripalimab (PD-1 antibody) to chemotherapy in patients with advanced ESCC regardless of PD-L1 status.
2. A meta-analysis of recent clinical trials on the use of PD-1 antibody plus chemotherapy as a first-line treatment for advanced ESCC in patients with low PD-L1 expression also found a positive effect.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Recent clinical trials have explored treatment options for advanced esophageal squamous cell carcinoma (ESCC) and established PD-1 antibody plus chemotherapy as a new standard treatment. However, there remains controversy if ESCC with low PD-L1 expression will have benefit from PD-1 antibody plus chemotherapy. This paper is a post hoc analysis of JUPITER-06 and a meta-analysis to assess the clinical benefit of PD-1 antibody plus chemotherapy in patients with low PD-L1 expression. The endpoints of this post hoc analysis included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and duration of response (DoR). PFS, OS, ORR, and DoR were longer in the toripalimab arm compared to the placebo in both PD-L1 subgroups. For the TPS≥1% group, the median PFS was 5.7 vs 5.5 months with an HR 0.59 while the median OS was 16.9 vs 10.8 months with an HR 0.61. For the TPS<1% group, the median PFS was 6.1 vs 5.7 months with an HR 0.59 while the median OS was unreached vs 11.6 months with an HR 0.63. This study also conducted a meta-analysis of five papers that examined the clinical benefit of adding PD-L1 antibody to chemotherapy in patients with advanced ECSS with low PD-L1 expression. The pooled analysis found the OS and PFS in patients with TPS <1% had HR 0.74 and 0.66 respectively. Similar results were seen when pooling patients with CPS<10. The strengths of this paper included analyzing data from various sources, and the limitations of this study included the heterogeneity of the papers included in the meta-analysis. Overall the post hoc analysis and the meta-analysis suggests that adding PD-1 antibody to chemotherapy as a first-line treatment for patients with advanced ESCC with low PD-L1 expression had positive effects.
Click to read the study in JCO
Relevant Reading: Toripalimab plus chemotherapy in treatment-naïve, advanced esophageal squamous cell carcinoma (JUPITER-06): A multi-center phase 3 trial
In-Depth [meta-analysis]: This study is a post hoc analysis of the PD-L1 tumor proportion score (TPS) across subgroups in a recent multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating PD-1 antibody (toripalimab) plus chemotherapy (paclitaxel and cisplatin) vs placebo plus chemotherapy as a first-line treatment of advanced ECSS. They found that TPS was strongly correlated with a combined positive score (CPS), R=0.86 (05%CI, 0.83 to 0.89, p<0.0001). PFS and OS were longer in the toripalimab arm compared to the placebo in both PD-L1 subgroups. Median PFS was 5.7 vs 5.5 months [HR 0.59 (95%CI, 0.44 to 0.79, p=0.0005)] while median OS was 16.9 vs 10.8 months [HR 0.61 (95%CI, 0.42 to 0.90, p=0.0133] in the TPS≥1% group. Median PFS was 6.1 vs 5.7 months [HR 0.59 (95%CI, 0.40 to 0.88, p= 0.0089) while median OS was unreached vs 11.6 months [HR 0.63 (95%CI, 0.37 to 1.08, p=0.0913) in the TPS <1% group. ORR was 65.6% versus 52.5% and 74.4% versus 54.4% in the TPS≥1% and TPS<1% subgroups, and DoR similarly showed improvement regardless of the TPS status. The above results were also seen when using 5% or 10% as the TPS cutoff. This study also conducted a meta-analysis of randomized control trials (RCTs) from PubMed, Embase, and Cochrane published from January 1st 2010 to April 30th 2022 that examined the clinical benefit of adding PD-L1 antibody to chemotherapy in patients with advanced ECSS with low PD-L1 expression. 719 studies were found, and 5 eligible studies were included in the meta-analysis. The pooled analysis found the OS and PFS in patients with TPS <1% had HR 0.74 (95%CI, 0.56 to 0.97, p=0.0312) and 0.66 (95%CI, 0.50 to 0.86; p=0.0027), respectively. Similar results were seen when pooling patients with CPS<10. Overall this data suggests that adding PD-1 antibody to chemotherapy as a first-line treatment for patients with advanced ESCC with low PD-L1 expression had positive effects.
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